Alkali-metal salts of mercuri-brom-fluorescein



@Patented Jan. 13, 1931 y UNITED STATES PATENT OFFICE,

WILLARD L. VOG-EL, OF LOS ANGELES, CALIFORNIA, ASSIGNOR OF ONE-TEN TH TO PAUL W. PRUTZMAN ALKALI-METAL SALTS OF MERCURI- BROM-FLUORESCEIN No Drawing. Original application filed May 28, 1928, Serial No. 281,355. Divided an d this application filed September 24, 1929.

The object of my invention is to produce a heretofore unknown mono-brom derivative of fluorescein and a heretofore unknown mercuric derivative of the said mono-brom compound. This mercury derivative may in turn be converted into a tetra-salt of an alkali metal, the tetra-sodium salt in particular having highly valuable properties as an antiseptic and therapeutic agent.

My invention comprises three steps: The hromination of fluorescein under such conditions as to produce the mono-brom derivative instead of the di-brom or tetra-brom derivatives heretofore known; the conversion of the mono-brom compound into a di-inercury derivative, and the conversion of the mercury derivative into a salt of an alkali metal.

The first step is taken in the following manner. To one molecule or 332 parts by weight of fluorescein I add approximately 660 parts of glacial acetic acid bring the fluorescein into even suspension and add gradually one molecule or 160 parts by weight of bromin (Br Copious fumes of hydrobromic acid are given ofl and agitation is continued at normal temperature until these fumes cease. The mixture is now allowed to stand for a short time, or until a pasty yellow cake is formed. This operation must be conducted in glass or equivalent vessel.

I next add to the cake about 1,000 parts by weight of water and stir until the cake is broken up, finally adding and intermixing an additional 3,200 parts of water. The thick yellow magma thus produced is then filtered by suction,washed with water, sucked as dry as possible, and finally transferred to a drying dish of porcelain or similar material, over the surface of which it is thinly distributed. The material is then heated on a sand or oil bath to a temperature not to exceed (3., the acetic acid which separates being poured off from time to time, and drying continued at the same temperature until a Serial No. 394,927.

dry material which, when powdered, is free I then proceed to the second step in the following manner. I first dissolve and reprecipitate the bromo-compound by mixing l molecules or 462 parts by weight in a glass Vessel with 2% molecules or 90 parts by weight of sodium hydroxid dissolved in say 500 parts by weight of water. I then add with constant stirring 2 1; molecules orparts by Weight of glacial acetic acid, by whlch a yellowprecipitate is formed.

In a separate vessel I prepare a solution of mercuric acetate by dissolving" 2% mole cules or 460 parts by weight of red mercuricoxid (HgO) in 8 molecules or 480 parts by weight of glacial acetic acid diluted'with 1,000 parts or water. Heat is applied until a clear solution is obtained, which is further diluted and filtered.

This solution is added to the reprecipitated bronio-comp-ound and the mixture diluted with approximately an equal volume of water. This mixture is then boiled under orate at about 6., or at the lowest pram ture of this body and the reaction by whicn it is formed appear to be as follows:

M onobromdihydroximercurifluorescein M.W. 810.2 2(CH3COOILCH3C O0) 238 The yieldot the inercuriated product is approximately eighty percent of the quan- 4 tity calculated from-the addition of mercury to the bromo-conipound.

The final step in my inventionis the preparation of an alkali metal salt of the above mercuric compound. This is formed by direct addition, one molecule or 810 parts by weight of the mercuric compound, and four molecules of a monatomic alkali (160 parts by weight if sodium hydroxid) are dissolved in 3600 parts ofpure methyl alcohol and stirred with gentleheating. The solution is then evaporated slowly to dryness and the dry melt powdered andstored in absolutely dry glass bottles.

If the melt is noted to contain any red particles it is redissolved in water and again evaporated to dryness. It is desirable to use glass beads to )lGVClll) spatterin and to evapticable temperature.

The tetra-sodium compound thus produced is a brassy green powder, slightly crystalline and highly hygroscopic. It is soluble in a small proportion of water, yielding a deep carmine red solution which on extreme dilution becomes a rich orange. The solution shows a strong green fluorescence and stains the skin bright red. on heating has no definite melting point.

Chemically the sodium salt is tetrasodium- V dihydroxymercurl monobrom fiuorescem,

empirical formula C H O B1'(I-IgOl-l) {la molecular weight 898.2. The position of the sodium atoms is not known with certainty, but as only the tetra salt is formed it is probable that they are symmetrical in the two res-orcinol rings and that the structure is as indicated below.

The salts of the alkali metals, and in particular the sodium salt, are powerful and 5 The salt decomposes non-irritating local antiseptics and preventives of infection.

H i H C H HgOH C n HgOH Na HgOH Mouobromdihydroximercurifluorescein M. W. 8102 4 NaOH 4 W. 160

Tctrasodiummonobromdihydroximercurifluorescien M. W. 898.2 4 H2O 72 This is a division of my co-pending application entitled Mercury bromin derivatives of fluorescein, Serial No. 233L355, liled May 28, 1928, Patent Number 1,749,201.

I claim as'my invention 1. The herein described product: the tetrasodium salt of the dime'rcury derivative of monobromfiuorescein.

2. The herein described product: tetrasodiumanono-broni-dihydr-oxi inercuri-fluorescein, having the" empirical formula C H O Brl-Ta (HgOH) 3. The herein described products, comprisingi' the alkali metal salts of the dimercury derivative of monobrom-fluorescein.

In witness that T claim the "for have hereunto subscribed my name t, day of August, 1929.

' \VILLARD L. VOGEL. 

